TY - JOUR
T1 - Enhancement of humoral immune responses against viral vaccines by a non-pyrogenic 6-O-acyl-muramyldipeptide and synthetic low toxicity analogues of lipid A
AU - Tsujimoto, Masachika
AU - Kotani, Shozo
AU - Okunaga, Takafumi
AU - Kubo, Takao
AU - Takada, Haruhiko
AU - Kubo, Takasi
AU - Shiba, Tetsuo
AU - Kusumoto, Shoichi
AU - Takahashi, Takashi
AU - Goto, Yoji
AU - Kinoshita, Fumio
N1 - Funding Information:
The authors are grateful to A. Inoue and S. Yokoyama (Daiichi Seiyaku Co. Ltd) and Dr L. Chedid (Institut Pasteur) for their generosity in providing the lipophilic derivatives of muramyl dipeptides. They are also grateful to M. Kato, Z. Tada and J. Osame (Kanonji Institute, Research Foundation for Microbial Disease of Osaka University) for their technical support and for providing influenza split and subunit vaccines. This work was supported in part by Grants-in-Aid for Scientific Research (Nos 60108005, 59771292, 59116005 and 58122007) from the Ministry of Education, Science and Culture of Japan.
PY - 1989/2
Y1 - 1989/2
N2 - 6-O-Acyl derivatives of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) and synthetic, low toxicity lipid-A analogues were examined for their ability to enhance the potency of current viral vaccines. 6-O-(2-Tetradecylhexadecanoyl)-MDP (B30-MDP) in non-irritative vehicles such as physiological saline, phosphate-buffered saline (PBS), squalene-PBS emulsion, Intralipid or liposomes, significantly stimulated the primary and secondary antibody production of guinea-pigs against influenza split or subunit vaccine and inactivated the hepatitis B virus surface (HBs) antigen. Mice seemed less responsive to the adjuvanticity of B30-MDP than guinea-pigs. Two low toxicity lipid A analogues, acylated β(1-6)-d-glucosamine disaccharide bisphosphates (which do not have amide-bound or ester-bound 3-acyloxyacyl groups unlike fully toxic Escherichia coli-type lipid A), caused significantly enhanced antibody responses, primary or secondary, when administered to mice by incorporation into liposomes with inactivated HBs antigen.
AB - 6-O-Acyl derivatives of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) and synthetic, low toxicity lipid-A analogues were examined for their ability to enhance the potency of current viral vaccines. 6-O-(2-Tetradecylhexadecanoyl)-MDP (B30-MDP) in non-irritative vehicles such as physiological saline, phosphate-buffered saline (PBS), squalene-PBS emulsion, Intralipid or liposomes, significantly stimulated the primary and secondary antibody production of guinea-pigs against influenza split or subunit vaccine and inactivated the hepatitis B virus surface (HBs) antigen. Mice seemed less responsive to the adjuvanticity of B30-MDP than guinea-pigs. Two low toxicity lipid A analogues, acylated β(1-6)-d-glucosamine disaccharide bisphosphates (which do not have amide-bound or ester-bound 3-acyloxyacyl groups unlike fully toxic Escherichia coli-type lipid A), caused significantly enhanced antibody responses, primary or secondary, when administered to mice by incorporation into liposomes with inactivated HBs antigen.
KW - 6-O-acylmuramyldipeptide
KW - N-Acetylmuramyl-l-alanyl-d-isoglutamine
KW - hepatitis B virus vaccine
KW - influenza split vaccine
KW - influenza subunit vaccine
KW - low toxicity lipid-A analogues
KW - muramyldipeptide
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U2 - 10.1016/0264-410X(89)90009-1
DO - 10.1016/0264-410X(89)90009-1
M3 - Article
C2 - 2718605
AN - SCOPUS:0024532160
VL - 7
SP - 39
EP - 48
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 1
ER -
